Johnson started his career as a lawyer representing many people for free. He was elected to the United States House of Representatives in 1806. During the War of 1812, Johnson led troops against the British.

Johnson later served in the Senate before being chosen as vice president. Johnson was elected by the Senate and not through the normal election because he did not have enough electors to win. This happened because Johnson lived with a slave named Julia Chinn, had two children with her, and treated her like his wife.

Johnson was not chosen to run with Van Buren in 1840. Johnson served in the Kentucky House of Representatives again as well as ran for a Senate seat again. In 1850 he was elected to the United States House of Representatives again but died two weeks into his term on November 19, 1850.